Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue

Kanjiro Miyata, Makoto Oba, Mitsunobu Kano, Shigeto Fukushima, Yelena Vachutinsky, Muri Han, Hiroyuki Koyama, Kohei Miyazono, Nobuhiro Nishiyama, Kazunori Kataoka

Research output: Contribution to journalArticle

40 Citations (Scopus)


Purpose. For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods. The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.

Original languageEnglish
Pages (from-to)2924-2936
Number of pages13
JournalPharmaceutical Research
Issue number12
Publication statusPublished - Dec 2008
Externally publishedYes



  • Gene delivery
  • PEG
  • Polyplex micelle
  • TGF-β inhibitor
  • Triblock copolymer

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

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